Critical analysis and validation of lymph node density as prognostic variable in urothelial carcinoma of bladder

ObjectiveTo validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer.MethodsFrom 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report.ResultsMedian age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11–32), median number of positive lymph nodes was 2 (IQR, 1–5), and median LND was 14.3% (IQR, 6.67–33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P < 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%–41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not.ConclusionLymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease.